Sensory impairment in older adults is associated with cognitive decline, elevated depressive symptoms, and low levels of life satisfaction. However, these relationships are usually investigated ...separately and in pairs. This study examined these relationships comprehensively, for the first time.
The analysis included 5,658 community-dwelling older adults from the China Health and Retirement Longitudinal Study (aged 50 to 108 years, 52.1% male) who completed the Jorm Informant Questionnaire Cognitive Decline in the Elderly and the Center for Epidemiological Studies-Depression-short form. A questionnaire was used to collect information on hearing, visual status, and life satisfaction. Structural equation modelling was used to examine the direct and indirect relationships between these variables.
Self-reported hearing and vision problems are directly associated with cognitive decline and elevated depressive symptoms. In addition, hearing and vision problems are indirectly related to cognitive decline through elevated depressive symptoms. Although hearing and vision problems had no direct effect on life satisfaction, they were indirectly associated with life satisfaction through cognitive decline and depressive symptoms.
This study provides the first epidemiological evidence of the comprehensive relationships between hearing and vision problems, cognitive decline, depressive symptoms, and life satisfaction. When older adults report hearing and/or vision problems, clinicians and caregivers should be aware of the concurrence of declined cognition, elevated depressive symptoms, and compensated life satisfaction. Future studies should examine the causal relationships and potential mechanisms of these relationships.
In Chinese languages, tones are used to express the lexical meaning of words. It is therefore important to analyze the role of lexical tone in Chinese sentence recognition accuracy. There is a lack ...of research on the role of Cantonese lexical tones in sentence recognition accuracy. Therefore, this study examined the contribution of lexical tone information to Cantonese sentence recognition accuracy and its cognitive correlates in adults with normal hearing (NH). A text-to-speech synthesis engine was used to synthesize Cantonese daily-use sentences with each word carrying an original or a flat lexical tone, which were then presented to 97 participants in quiet, in speech-shaped noise (SSN), and in two-talker babble (TTB) noise conditions. Both target sentences and noises were presented at 65 dB binaurally via insert headphones. It was found that listeners with NH can almost perfectly recognize a daily-use Cantonese sentence with mismatched lexical tone information in quiet, while their sentence recognition decreases substantially in noise. The same finding was reported for Mandarin, which has a relatively simple tonal system, suggesting that the current results may be applicable to other tonal languages. In addition, working memory (WM) was significantly related to decline in sentence recognition score in the TTB but not in the SSN, when the lexical tones were mismatched. This finding can be explained using the Ease of Language Understanding model and suggests that those with higher WM are less likely to be affected by the degraded lexical information for perceiving daily-use sentences in the TTB.
Like classical block codes, a locally repairable code also obeys the Singleton-type bound (we call a locally repairable code optimal if it achieves the Singleton-type bound). In the breakthrough work ...of Tamo and Barg, several classes of optimal locally repairable codes were constructed via subcodes of Reed-Solomon codes. Thus, the lengths of the codes given by Tamo and Barg are upper bounded by the code alphabet size q. Recently, it was proved through the extension of construction by Tamo and Barg that the length of q-ary optimal locally repairable codes can be q +1 by Jin et al. Surprisingly, Barg et al. presented a few examples of q-ary optimal locally repairable codes of small distance and locality with code length achieving roughly q 2 . Very recently, it was further shown in the work of Li et al. that there exist q-ary optimal locally repairable codes with the length bigger than q+1 and the distance proportional to n. Thus, it becomes an interesting and challenging problem to construct new families of q-ary optimal locally repairable codes of length bigger than q+1. In this paper, we construct a class of optimal locally repairable codes of distances 3 and 4 with unbounded length (i.e., length of the codes is independent of the code alphabet size). Our technique is through cyclic codes with particular generator and parity-check polynomials that are carefully chosen.
Dysbiosis represents changes in composition and structure of the gut microbiome community (microbiome), which may dictate the physiological phenotype (health or disease). Recent technological ...advances and efforts in metagenomic and metabolomic analyses have led to a dramatical growth in our understanding of microbiome, but still, the mechanisms underlying gut microbiome-host interactions in healthy or diseased state remain elusive and their elucidation is in infancy. Disruption of the normal gut microbiota may lead to intestinal dysbiosis, intestinal barrier dysfunction, and bacterial translocation. Excessive uremic toxins are produced as a result of gut microbiota alteration, including indoxyl sulphate, p-cresyl sulphate, and trimethylamine-N-oxide, all implicated in the variant processes of kidney diseases development. This review focuses on the pathogenic association between gut microbiota and kidney diseases (the gut-kidney axis), covering CKD, IgA nephropathy, nephrolithiasis, hypertension, acute kidney injury, hemodialysis and peritoneal dialysis in clinic. Targeted interventions including probiotic, prebiotic and symbiotic measures are discussed for their potential of re-establishing symbiosis, and more effective strategies for the treatment of kidney diseases patients are suggested. The novel insights into the dysbiosis of the gut microbiota in kidney diseases are helpful to develop novel therapeutic strategies for preventing or attenuating kidney diseases and complications.
To report long‐term results of a randomized controlled trial that compared cisplatin/fluorouracil/docetaxel (TPF) induction chemotherapy (IC) plus concurrent chemoradiotherapy (CCRT) with CCRT alone ...in locoregionally advanced nasopharyngeal carcinoma (NPC). Patients with stage III–IVB (except T3–4 N0) NPC were randomly assigned to receive IC plus CCRT (n = 241) or CCRT alone (n = 239). IC included three cycles of docetaxel (60 mg/m2 d1), cisplatin (60 mg/m2 d1), and fluorouracil (600 mg/m2/d civ d1–5) every 3 weeks. Patients from both groups received intensity‐modulated radiotherapy concurrently with three cycles of 100 mg/m2 cisplatin every 3 weeks. After a median follow‐up of 71.5 months, the IC plus CCRT group showed significantly better 5‐year failure‐free survival (FFS, 77.4% vs. 66.4%, p = 0.019), overall survival (OS, 85.6% vs. 77.7%, p = 0.042), distant failure‐free survival (88% vs. 79.8%, p = 0.030), and locoregional failure‐free survival (90.7% vs. 83.8%, p = 0.044) compared to the CCRT alone group. Post hoc subgroup analyses revealed that beneficial effects on FFS were primarily observed in patients with N1, stage IVA, pretreatment lactate dehydrogenase ≥170 U/l, or pretreatment plasma Epstein–Barr virus DNA ≥6000 copies/mL. Two nomograms were further developed to predict the potential FFS and OS benefit of TPF IC. The incidence of grade 3 or 4 late toxicities was 8.8% (21/239) in the IC plus CCRT group and 9.2% (22/238) in the CCRT alone group. Long‐term follow‐up confirmed that TPF IC plus CCRT significantly improved survival in locoregionally advanced NPC with no marked increase in late toxicities and could be an option of treatment for these patients.
What's new?
Despite advances in the treatment of nasopharyngeal carcinoma, approximately 30% of high‐risk patients experience recurrence after treatment. Here the authors find that combining the conventional chemoradiotherapy with a triple induction chemotherapy (cisplatin/fluorouracil/docetaxel) prolonged survival of patients with locoregionally advanced cancer, even after more than 70 months of follow‐up. The combination treatment increased acute, but not late, toxicities, and the authors propose that it could present a new treatment option for this patient group.
The inside walls of a nanopipette tip are decorated by a Pt deposit that is used as an open bipolar electrochemiluminescence (ECL) device to achieve intracellular wireless electroanalysis. The ...synergetic actions of nanopipette and of bipolar ECL lead to the spatial confinement of the voltage drop at the level of the Pt deposit, which generates ECL emission from luminol. The porous structure of Pt deposit permits the electrochemical transport of intracellular molecules into the nanopipette that is coupled with enzymatic reactions. Thus, the intracellular concentrations of hydrogen peroxide or glucose are measured in vivo as well as the intracellular sphingomyelinase activity. In comparison with the classic bipolar ECL, the remarkably low potential applied in our approach is restricted inside the nanopipette and it minimizes the potential bias of the voltage on the cellular activity. Accordingly, this wireless ECL approach provides a new direction for analysis of single living cells.
A nanopipette tip decorated with a Pt deposit is used as an open bipolar electrochemiluminescence device to achieve intracellular wireless electroanalysis. The porous structure of the Pt deposit permits electrochemical transport of intracellular molecules into the nanopipette. Intracellular concentrations of H2O2 or glucose are measured in vivo as well as the intracellular sphingomyelinase activity.
Huntington's disease (HD) is a neurodegenerative disorder that manifests with movement dysfunction. The expression of mutant Huntingtin (mHTT) disrupts the functions of brain cells. Galectin-3 (Gal3) ...is a lectin that has not been extensively explored in brain diseases. Herein, we showed that the plasma Gal3 levels of HD patients and mice correlated with disease severity. Moreover, brain Gal3 levels were higher in patients and mice with HD than those in controls. The up-regulation of Gal3 in HD mice occurred before motor impairment, and its level remained high in microglia throughout disease progression. The cell-autonomous up-regulated Gal3 formed puncta in damaged lysosomes and contributed to inflammation through NFκB- and NLRP3 inflammasome-dependent pathways. Knockdown of Gal3 suppressed inflammation, reduced mHTT aggregation, restored neuronal DARPP32 levels, ameliorated motor dysfunction, and increased survival in HD mice. Thus, suppression of Gal3 ameliorates microglia-mediated pathogenesis, which suggests that Gal3 is a novel druggable target for HD.
Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic cancer featured with high intra-tumoral heterogeneity and poor prognosis. To comprehensively delineate the PDAC ...intra-tumoral heterogeneity and the underlying mechanism for PDAC progression, we employed single-cell RNA-seq (scRNA-seq) to acquire the transcriptomic atlas of 57,530 individual pancreatic cells from primary PDAC tumors and control pancreases, and identified diverse malignant and stromal cell types, including two ductal subtypes with abnormal and malignant gene expression profiles respectively, in PDAC. We found that the heterogenous malignant subtype was composed of several subpopulations with differential proliferative and migratory potentials. Cell trajectory analysis revealed that components of multiple tumor-related pathways and transcription factors (TFs) were differentially expressed along PDAC progression. Furthermore, we found a subset of ductal cells with unique proliferative features were associated with an inactivation state in tumor-infiltrating T cells, providing novel markers for the prediction of antitumor immune response. Together, our findings provide a valuable resource for deciphering the intra-tumoral heterogeneity in PDAC and uncover a connection between tumor intrinsic transcriptional state and T cell activation, suggesting potential biomarkers for anticancer treatment such as targeted therapy and immunotherapy.
Background and Purpose
Increasing evidence has indicated that the high risk of cardiovascular disease in chronic kidney disease (CKD) patients cannot be sufficiently explained by classic risk ...factors.
Experimental Approach
Based on the least absolute shrinkage and selection operator method, we identified significantly altered renal tissue metabolites during progressive CKD in a 5/6 nephrectomized rat model and in CKD patients.
Key Results
Six aryl‐containing metabolites (ACMs) were significantly increased from Week 1 to Week 20. They were associated with the activation of aryl hydrocarbon receptor (AhR) and its target genes including CYP1A1, CYP1A2 and CYP1B1, which were further validated by molecular docking. Our study further demonstrated that AhR signalling could be activated by ACM in patients with idiopathic membranous nephropathy, diabetic nephropathy and IgA nephropathy. Most importantly, 1‐aminopyrene (AP) showed strong positive and negative correlation with serum creatinine and creatinine clearance, respectively. AP significantly up‐regulated the mRNA expressions of AhR and its three target genes in both mice and NRK‐52E cells, while this effect was partially weakened in AhR small hairpin RNA‐treated mice and NRK‐52E cells. Furthermore, dietary flavonoid supplementation ameliorated CKD and renal fibrosis through partially inhibiting the AhR activity via lowering the ACM levels. The antagonistic effect of flavonoids on AhR was deeply influenced by the number and location of hydroxyl and glycosyl groups.
Conclusion and Implications
We uncovered that endogenous AP is a novel mediator of CKD progression via AhR activation; thus, AhR might serve as a promising target for CKD treatment.
In elderly people particularly in postmenopausal women, inadequate bone formation by osteoblasts originating from bone marrow mesenchymal stem cells (BMSCs) for compensation of bone resorption by ...osteoclasts is a major reason for osteoporosis. Enhancing osteoblastic differentiation of BMSCs is a feasible therapeutic strategy for osteoporosis. Here, bone marrow stromal cell (ST)-derived exosomes (STExos) are found to remarkably enhance osteoblastic differentiation of BMSCs in vitro. However, intravenous injection of STExos is inefficient in ameliorating osteoporotic phenotypes in an ovariectomy (OVX)-induced postmenopausal osteoporosis mouse model, which may be because STExos are predominantly accumulated in the liver and lungs, but not in bone. Hereby, the STExo surface is conjugated with a BMSC-specific aptamer, which delivers STExos into BMSCs within bone marrow. Intravenous injection of the STExo-Aptamer complex enhances bone mass in OVX mice and accelerates bone healing in a femur fracture mouse model. These results demonstrate the efficiency of BMSC-specific aptamer-functionalized STExos in targeting bone to promote bone regeneration, providing a novel promising approach for the treatment of osteoporosis and fracture.
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